Colposcopy is a standard technique to detect early neoplastic growth in cervical tissue. It is a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva. Many premalignant lesions and malignant lesions in these areas have discernible characteristics which can be detected through this examination technique. It is done using a colposcope, which provides an enlarged view of the areas under examination, allowing the colposcopist to visually distinguish normal from abnormal appearing tissue and take directed biopsies for further pathological examination. The main goal of colposcopy is to prevent cervical cancer by detecting precancerous lesions early and treating them.
Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the potentially premalignant transformation and abnormal growth (i.e., dysplasia) of squamous cells on the surface of the cervix. Most cases of CIN remain stable, or are eliminated by the host's immune system without intervention. However a small percentage of cases progress to become cervical cancer, usually cervical squamous cell carcinoma (SCC), if left untreated. The major cause of CIN is chronic infection of the cervix with the sexually transmitted human papillomavirus (HPV), especially the high-risk HPV types 16 or 18. Over 100 types of HPV have been identified. About a dozen of these types appear to cause cervical dysplasia & may lead to the development of cervical cancer.
Principles of the colposcopy involve the use of acetic acid, to induce an acetowhitening effect in tissues and to produce the contrast between normal tissues and precancerous lesions for diagnosis. Specifically, acetic acid causes swelling of the epithelial tissue, columnar and any abnormal squamous epithelial areas in particular, leading to a reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Thus, the effect of acetic acid depends upon the amount of nuclear proteins and cytokeratins present in the epithelium. When acetic acid is applied to normal squamous epithelium, little coagulation occurs in the superficial cell layer, as this is sparsely nucleated. Though the deeper cells contain more nuclear protein, the acetic acid may not penetrate sufficiently and, hence, the resulting precipitation is not sufficient to obliterate the color of the underlying stroma.
Areas of the cervical CIN undergo maximal coagulation due to their higher content of nuclear protein and prevent light from passing through the epithelium. As a result, the subepithelial vessel pattern is obliterated, and less easy to see, and the epithelium appears white. This reaction is termed acetowhitening, and produces a noticeable effect compared with the normal pinkish color of the surrounding normal squamous epithelium of the cervix, an effect that is commonly visible to the naked eye.
Part of the colposcopic process involves grading the CIN. Depending on several factors such as the type of HPV and the location of the infection, the CIN can be classified into one of the three grades. CIN1 (Grade I) indicates the least risky type, representing only mild dysplasia, or abnormal cell growth. This grade corresponds to a low grade squamous intraepithelial lesion result on a Pap test. This corresponds to infection with HPV, and typically will be cleared by immune response in a year or so, though can take several years to clear. CIN2 (Grade II) indicates moderate dysplasia confined to the basal ⅔ of the epithelium. CIN3 (Grade III) indicates severe dysplasia that spans more than ⅔ of the epithelium and may involve the full thickness. This lesion may sometimes also be referred to as cervical carcinoma in situ.
With low-grade CIN, the acetic acid must penetrate into the lower one-third of the epithelium (where most of the abnormal cells with high nuclear density are located). Hence, the appearance of the whiteness is delayed and less intense due to the smaller amount of nuclear protein compared to areas with high-grade CIN or preclinical invasive cancer. Areas of high-grade CIN and invasive cancer turn densely white and opaque immediately after application of acetic acid, due to their higher concentration of abnormal nuclear protein and the presence of large numbers of dysplastic cells in the superficial layers of the epithelium.
Acetowhitening associated with CIN and invasive cancer quickly appears and persists for more than one minute. The acetic acid effect reverses much more slowly in high-grade CIN lesions and in early pre-clinical invasive cancer than in low-grade lesions, immature metaplasia changes. It may last for 2-4 minutes in the case of high-grade lesions and invasive cancer.
As previously stated, the main goal of colposcopy is to detect the presence of high-grade CIN and invasive cancer. To effectively achieve this, the entire epithelium at risk should be well visualized, abnormalities should be identified accurately and assessed for their degree of abnormality, and appropriate biopsies must be taken. The colposcopic documentation and the biopsies taken by a colposcopist are important indicators for quality management in colposcopy clinics.
The diagnostic criteria of colposcopy based on acetowhitening are subjectively related to the following parameters: the rapidity and length of the acetowhitening processes, the degree of acetowhiteness when the change of color reaches maximum, and the sharpness of the demarcation line between the precancerous lesions and normal tissues. The diagnostic accuracy depends on how an individual colposcopist applies these guidelines during the diagnosis. Therefore, an objective diagnostic procedure based on quantitative measurement of the acetowhitening process is desirable.
The dynamic process of acetowhitening can assist in discriminating the normal and abnormal cervical tissue, even for distinguishing the different grades of CIN. However, as the patient does not reliably remain completely stationary and the camera may be moved by the colposcopist during the colposcopy procedure, which normally takes several minutes, the pixel coordinates of the area of interest in time-sequenced images will change. Slight motion of the patient will cause the loss of the correspondence between the time-sequenced images of cervix recorded during the examination. Without image registration prevented by movement of the patient and/or camera, the measurement of acetowhitening kinetics using the time-sequenced images generates false diagnostic information. Therefore, accurate registration of the time-sequenced images during colposcopy procedure is crucial for accurately measuring the kinetics of acetowhitening in the area of interest.
In image registration for compensating the patient motions during medical diagnosis, it is ideal to make use of the natural features, such as the external Os region (i.e., the opening of the ectocervix) and the transformation zone, for the purpose of image tracking and registration. However, it has been found that these features are not reliable and lack contrasts. For example, the Os is located in the center of the cervix. But it is not always open and its boundary is generally not clear. What is more, previous studies show that the boundary between the transformation zone and the ectocervix is generally not clear. A common approach to visualize the boundary is to apply acetic acid to generate the contrast between the transformation zone and the ectocervix. However, the boundary fades away quickly as the decay of the contrast is induced by the applied acetic acid. This makes the features of the transformation zone unreliable for motion tracking.
Furthermore, because most of the lesions develop within or near the transformation zone, after the acetic acid is applied, the whitened tissue areas (i.e., the CIN lesions) introduce severe interferences and errors to identifying the boundaries of the Os and transformation zone. Therefore, even though the boundaries of the Os and the transformation zone can be identified in some cases, these features are not reliable because they overlap with the acetowhitened tissue areas that are constantly changing during the acetowhitening process. Moreover, due to the patient's motion, three-dimensional rotations cannot be compensated for by using the rigid two-dimensional image registration. Non-rigid image registration may correct the errors caused by the three-dimensional rotation. However, it is much more complicated and may induce more errors than the rigid method.